Abduction treatment in stable hip dysplasia does not alter the acetabular growth: results of a randomized clinical trial.

Background The effect of bracing over natural history of stable dysplastic hips is not well known. This multicenter randomized trial aimed at objectifying the effect of abduction treatment versus active surveillance in infants of 3 to 4 months of age. Methods Patients were randomized to either Pavlik harness or active surveillance group. Ultrasound was repeated at 6 and 12 weeks post randomization. The primary outcome was the degree of dysplasia using the Graf α-angle at 6 months of age. The measurement of the acetabular index (AI) on plain pelvis X-rays was used to identify persistent dysplasia after 9 months and walking age (after 18 months). Findings The Pavlik harness group (n = 55) and active surveillance group (n = 49) were comparable for predictors of outcome. At 12 weeks follow-up the mean α-angle was 60.5° ± 3.8° in the Pavlik harness group and 60.0° ± 5.6° in the active surveillance group. (p = 0.30). Analysis of secondary outcomes (standard of care) showed no treatment differences for acetabular index at age 10 months (p = 0.82) and walking age (p = 0.35). Interpretation Pavlik harness treatment of stable but sonographic dysplastic hips has no effect on acetabular development. Eighty percent of the patients will have a normal development of the hip after twelve weeks. Therefore, we recommend observation rather than treatment for stable dysplastic hips.

Cardiometabolic health in offspring of women with PCOS compared to healthy controls: a systematic review and individual participant data meta-analysis.

BACKGROUND: Women diagnosed with polycystic ovary syndrome (PCOS) suffer from an unfavorable cardiometabolic risk profile, which is already established by child-bearing age. OBJECTIVE AND RATIONALE: The aim of this systematic review along with an individual participant data meta-analysis is to evaluate whether cardiometabolic features in the offspring (females and males aged 1-18 years) of women with PCOS (OPCOS) are less favorable compared to the offspring of healthy controls. SEARCH METHODS: PubMed, Embase and gray literature databases were searched by three authors independently (M.N.G., M.A.W and J.C.) (last updated on 1 February 2018). Relevant key terms such as 'offspring' and 'PCOS' were combined. Outcomes were age-specific standardized scores of various cardiometabolic parameters: BMI, blood pressure, glucose, insulin, lipid profile and the sum scores of various cardiometabolic features (metabolic sum score). Linear mixed models were used for analyses with standardized beta (ß) as outcome. OUTCOMES: Nine relevant observational studies could be identified, which jointly included 1367 children: OPCOS and controls, originating from the Netherlands, Chile and the USA. After excluding neonates, duplicate records and follow-up screenings, a total of 885 subjects remained. In adjusted analyses, we observed that OPCOS (n = 298) exhibited increased plasma levels of fasting insulin (ß = 0.21(95%CI: 0.01-0.41), P = 0.05), insulin-resistance (ß = 0.21(95%CI: 0.01-0.42), P = 0.04), triglycerides (ß = 0.19(95%CI: 0.02-0.36), P = 0.03) and high-density lipoprotein (HDL)-cholesterol concentrations (ß = 0.31(95%CI: 0.08-0.54), P < 0.01), but a reduced birthweight (ß = -116(95%CI: -195 to 38), P < 0.01) compared to controls (n = 587). After correction for multiple testing, however, differences in insulin and triglycerides lost their statistical significance. Interaction tests for sex revealed differences between males and females when comparing OPCOS versus controls. A higher 2-hour fasting insulin was observed among female OPCOS versus female controls (estimated difference for females (ßf) = 0.45(95%CI: 0.07 to 0.83)) compared to the estimated difference between males ((ßm) = -0.20(95%CI: -0.58 to 0.19)), with interaction-test: P = 0.03. Low-density lipoprotein-cholesterol differences in OPCOS versus controls were lower among females (ßf = -0.39(95%CI: -0.62 to 0.16)), but comparable between male OPCOS and male controls (ßm = 0.27(95%CI: -0.03 to 0.57)), with interaction-test: P < 0.01. Total cholesterol differences in OPCOS versus controls were also lower in females compared to the difference in male OPCOS and male controls (ßf = -0.31(95%CI: -0.57 to 0.06), ßm = 0.28(95%CI: -0.01 to 0.56), interaction-test: P = 0.01). The difference in HDL-cholesterol among female OPCOS versus controls (ßf = 0.53(95%CI: 0.18-0.88)) was larger compared to the estimated mean difference among OPCOS males and the male controls (ßm = 0.13(95%CI: -0.05-0.31), interaction-test: P < 0.01). Interaction test in metabolic sum score revealed a significant difference between females (OPCOS versus controls) and males (OPCOS versus controls); however, sub analyses performed in both sexes separately did not reveal a difference among females (OPCOS versus controls: ßf = -0.14(95%CI: -1.05 to 0.77)) or males (OPCOS versus controls: ßm = 0.85(95%CI: -0.10 to 1.79)), with P-value < 0.01. WIDER IMPLICATIONS: We observed subtle signs of altered cardiometabolic health in OPCOS. Therefore, the unfavorable cardiovascular profile of women with PCOS at childbearing age may-next to a genetic predisposition-influence the health of their offspring. Sensitivity analyses revealed that these differences were predominantly observed among female offspring aged between 1 and 18 years. Moreover, studies with minimal risk of bias should elucidate the influence of a PCOS diagnosis in mothers on both sexes during fetal development and subsequently during childhood.

Correlation between ultrasonic and radiographic imaging of developmental dysplasia of the hip.

PURPOSE: The correlation between the degree of developmental hip dysplasia (DDH) measured on ultrasound images compared with that measured on radiographs is not clear. Most studies have compared ultrasonography (US) and radiographic images made at different times of follow-up. In this study the correlation between US images and radiographs of the hip made on the same day was evaluated. METHODS: US images and radiographs of both hips of 74 infants, who were treated for stable DDH, were reviewed in a retrospective study. Only infants who had an US examination and a radiograph on the same day were included. RESULTS: The correlation between α-angle of Graf and femoral head coverage on US was strong (p ≤ 0.0001). Weak correlations were found between the acetabular index of Tönnis on radiographs and α-angle of Graf on US (p = 0.049) and between acetabular index of Tönnis on radiographs and femoral head coverage of Morin on US (p = 0.100). CONCLUSION: This study reports on the correlation between US and radiographic imaging outcomes, both made on the same day in patients for treatment and follow-up of DDH. LEVEL OF EVIDENCE: IV.

Excess early postnatal weight gain and blood pressure in healthy young children.

Blood pressure (BP) tracks from childhood to adulthood, and early BP trajectories predict cardiovascular disease risk later in life. Excess postnatal weight gain is associated with vascular changes early in life. However, to what extent it is associated with children's BP is largely unknown. In 853 healthy 5-year-old children of the Wheezing-Illnesses-Study-Leidsche-Rijn (WHISTLER) birth cohort, systolic (SBP) and diastolic BP (DBP) were measured, and z scores of individual weight gain rates adjusted for length gain rates were calculated using at least two weight and length measurements from birth until 3 months of age. Linear regression analyses were conducted to investigate the association between weight gain rates adjusted for length gain rates and BP adjusted for sex and ethnicity. Each standard deviation increase in weight gain rates adjusted for length gain rates was associated with 0.9 mmHg (95% CI 0.3, 1.5) higher sitting SBP after adjustment for confounders. Particularly in children in the lowest birth size decile, high excess weight gain was associated with higher sitting SBP values compared to children with low weight gain rates adjusted for length gain rates. BMI and visceral adipose tissue partly explained the association between excess weight gain and sitting SBP (ß 0.5 mmHg, 95% CI -0.3, 1.3). Weight gain rates adjusted for length gain rates were not associated with supine SBP or DBP. Children with excess weight gain, properly adjusted for length gain, in the first three months of life, particularly those with a small birth size, showed higher sitting systolic BP at the age of 5 years.

Childhood infections and common carotid intima media thickness in adolescence.

Atherosclerotic changes can be measured as changes in common carotid intima media thickness (CIMT). It is hypothesised that repeated infection-associated inflammatory responses in childhood contribute to the atherosclerotic process. We set out to determine whether the frequency of infectious diseases in childhood is associated with CIMT in adolescence. The study is part of the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) population-based birth cohort. At age 16 years, common CIMT was measured. We collected general practitioner (GP) diagnosed infections and prescribed antibiotics. Parent-reported infections were retrieved from annual questionnaires. Linear regression analysis assessed the association between number of infections during the first 4 years of life and common CIMT. Common CIMT measurement, GP and questionnaire data were available for 221 participants. No association was observed between the infection measures and CIMT. In a subgroup analysis, significant positive associations with CIMT were observed in participants with low parental education for 2-3 or ⩾7 GP diagnosed infections (+26.4 µm, 95% CI 0.4-52.4 and +26.8 µm, 95% CI 3.6-49.9, respectively) and ⩾3 antibiotic prescriptions (+35.5 µm, 95%CI 15.8-55.3). Overall, early childhood infections were not associated with common CIMT in adolescence. However, a higher number of childhood infections might contribute to the inflammatory process of atherosclerosis in subgroups with low education, this needs to be confirmed in future studies.

[Systematic detection of physical child abuse at emergency rooms]. / Screening op kindermishandeling op de SEH.

OBJECTIVE: The aim of our diagnostic accuracy study Child Abuse Inventory at Emergency Rooms (CHAIN-ER) was to establish whether a widely used checklist accurately detects or excludes physical abuse among children presenting to ERs with physical injury. DESIGN: A large multicentre study with a 6-month follow-up in 4 ERs in The Netherlands. METHOD: Participants were 4290 children aged 0-7 years, attending the ER because of physical injury. All children were systematically tested with an easy-to-use child abuse checklist (index test). A national expert panel (reference standard) retrospectively assessed all children with positive screens and a 15% random sample of the children with negative screens for physical abuse, using additional information, namely, an injury history taken by a paediatrician, information provided by the general practitioner, youth doctor and social services by structured questionnaires, and 6-month follow-up information. Our main outcome measure was physical child abuse; secondary outcome measure was injury due to neglect and need for help. RESULTS: 4253/4290 (99%) parents agreed to follow-up. At a prevalence of 0.07% (3/4253) for inflicted injury by expert panel decision, the positive predictive value of the checklist was 0.03 (95% CI 0.006 to 0.085), and the negative predictive value 1.0 (0.994 to 1.0). There was 100% (93 to 100) agreement about inflicted injury in children, with positive screens between the expert panel and child abuse experts. CONCLUSION: Rare cases of inflicted injury among preschool children presenting at ERs for injury are very likely captured by easy-to-use checklists, but at very high false-positive rates. Subsequent assessment by child abuse experts can be safely restricted to children with positive screens at very low risk of missing cases of inflicted injury. Because of the high false positive rate, we do advise careful prior consideration of cost-effectiveness and clinical and societal implications before de novo implementation.

Adiponectin and incident coronary heart disease and stroke. A systematic review and meta-analysis of prospective studies.

The plasma concentration of adiponectin, an adipokine that has anti-inflammatory, anti-atherogenic and insulin sensitizing properties, is lower in obese subjects and could therefore be a target for therapy. In order to review and meta-analyse prospective cohort studies investigating adiponectin concentration and the risk for incident coronary heart disease (CHD) or stroke, a systematic search of MEDLINE, EMBASE and Cochrane databases was performed. Two independent reviewers selected prospective cohort studies investigating the relationship between adiponectin level and incident CHD or stroke using 'adiponectin' and 'cardiovascular disease' or 'stroke' and their synonyms, excluding patients with clinically manifest vascular disease. Random-effects models were used to calculate pooled relative risks (RRs) and 95% confidence intervals (95% CI). Generalized least squares regression was used to assess dose-response relationships for adiponectin concentrations from studies that provided RRs solely based upon categorical data regression. In total, 16 prospective cohort studies, comprising 23,919 patients and 6,870 CHD or stroke outcome events, were included in the meta-analyses. An increase of 1 standard deviation in log-transformed adiponectin did not lower the risk for CHD (RR 0.97; 95% CI 0.86-1.09). A 10 µg mL(-1) increase in adiponectin conferred a RR of 0.91 (95% CI 0.80-1.03) for CHD and a RR 1.01 (95% CI 0.97-1.06) for stroke. In conclusion, plasma adiponectin is not related to the risk for incident CHD or stroke.

Rapid early weight gain is associated with wheeze and reduced lung function in childhood.

The aim of our study was to investigate the association between rapid weight gain in the first 3 months of life and the prevalence of wheeze in the first years of life and lung function at 5 yrs of age. The infants selected were participating in an ongoing birth cohort. Information on growth and respiratory symptoms was collected during the first year of life, and on primary care consultations during total follow-up. Forced expiratory volume in 1 s (FEV(1)) and forced expiratory flow at 25-75% of forced vital capacity (FEF(25-75%)) were measured at 5 yrs of age. Information on growth and respiratory symptoms was obtained for 1,431 infants, out of whom 235 children had already had 5 yrs of follow-up. Every one-point z-score increase in weight gain resulted in a 37% increase in days with wheeze (incidence rate ratio 1.37, 95% CI 1.27-1.47; p<0.001) and in associated consultations by 16% (incidence rate ratio 1.16, 95% CI 1.01-1.34; p=0.04). Children with rapid weight gain reported significantly more physician-diagnosed asthma. FEV(1) and FEF(25-75%) were reduced by 34 mL (adjusted regression coefficient -0.034, 95% CI -0.056- -0.013; p=0.002) and 82 mL (adjusted regression coefficient -0.082, 95% CI -0.140- -0.024; p=0.006) per every one-point z-score increase in weight gain, respectively. These associations were independent of birthweight. Rapid early weight gain is a risk factor for clinically relevant wheezing illnesses in the first years of life and lower lung function in childhood.

The risk of general and abdominal adiposity in the occurrence of new vascular events and mortality in patients with various manifestations of vascular disease.

AIMS: Adiposity is associated with an increased but also with a decreased risk for successive vascular events or mortality in patients with different manifestations of vascular disease. In this study we directly compare the risk of general adiposity or abdominal obesity on the occurrence of new vascular events or mortality in these patients. METHODS: Patients with cerebrovascular disease (CVD; n=973), coronary artery disease (CAD; n=2339) or peripheral arterial disease (PAD; n=894) were prospectively followed for the occurrence of a vascular event or death. The median follow-up was 4.5 years. Adiposity was assessed with body mass index (BMI), waist circumference (WC) and determination of intra-abdominal fat through ultrasound. Cox proportional hazards models were used to evaluate the risk for new vascular events, vascular mortality and all-cause mortality. RESULTS: CAD patients had a 12% increased risk for vascular mortality with 1 BMI unit increase (hazard ratio (HR) 1.12; 95% confidence interval (CI) 1.05-1.20) and a 25% increased risk with 1cm increase in intra-abdominal adipose tissue (HR 1.25; 95% CI 1.12-1.39). The risk for all-cause mortality was increased by 3% (HR 1.03; 95% CI 1.01-1.05) with 1 cm increase in WC and was increased by 15% (HR 1.15; 95% CI 1.06-1.25) with 1 cm increase in intra-abdominal adipose tissue. In PAD patients there was an inverse relationship between BMI and vascular mortality (HR 0.93; 95% CI 0.87-0.98) and all-cause mortality (HR 0.90; 95% CI 0.86-0.94). In CVD patients there was no relation between obesity and vascular events or mortality. CONCLUSION: General adiposity is associated with an increased risk for vascular mortality in CAD patients and a decreased risk for (vascular) mortality in PAD patients.

Surgery in adults with congenital heart disease.

BACKGROUND: A significant proportion of patients with congenital heart disease require surgery in adulthood. We aimed to give an overview of the prevalence, distribution, and outcome of cardiovascular surgery for congenital heart disease. We specifically questioned whether the effects of surgical treatment on subsequent long-term survival depend on sex. METHODS AND RESULTS: From the Dutch Congenital Corvitia (CONCOR) registry for adults with congenital heart disease, we identified 10 300 patients; their median age was 33.1 years. Logistic and Cox regression models were used to assess the association of surgery in adulthood with sex and with long-term survival. In total, 2015 patients (20%) underwent surgery for congenital heart disease in adulthood during a median follow-up period of 15.1 years; in 812 patients (40%), it was a reoperation. Overall, both first operations and reoperations in adulthood were performed significantly more often in men compared with women (adjusted odds ratio=1.4 [95% confidence interval, 1.2-1.6] and 1.2 [95% confidence interval, 1.0-1.4], respectively). Patients with their third and fourth or more surgery in adulthood had a 2- and 3-times-higher risk of death compared with patients never operated on (adjusted hazard ratio=1.9 [95% confidence interval, 1.0-3.6] and 2.7 [95% confidence interval, 1.1-6.3], respectively). Men with a reoperation in adulthood had a 2-times-higher risk of death than women (adjusted hazard ratio=1.9; 95% confidence interval, 1.0-3.5). CONCLUSIONS: Of predominantly young adults with congenital heart disease, one fifth required cardiovascular surgery during a 15-year period; in 40%, the surgery was a reoperation. Men with congenital heart disease have a higher chance of undergoing surgery in adulthood and have a consistently worse long-term survival after reoperations in adulthood compared with women.

Relationship between parental lung function and their children's lung function early in life.

This study investigated the relationship between parental lung function and their children's lung function measured early in life. Infants were participants in the Wheezing Illnesses Study Leidsche Rijn (WHISTLER). Lung function was measured before the age of 2 months using the single occlusion technique. Parental data on lung function (spirometry), medical history and environmental factors were obtained from the linked database of the Utrecht Health Project. Parental data on pulmonary function and covariates were available in 546 infants. Univariate linear regression analysis demonstrated a significant positive relationship between the infant's respiratory compliance and parental forced expiratory flow at 25-75% of forced vital capacity (FEF(25-75%))(,) forced expiratory volume in 1 s (FEV(1)) and forced vital capacity. A significant negative relationship was found between the infant's respiratory resistance and parental FEF(25-75%)and FEV(1). No significant relationship was found between the infant's respiratory time constant and parental lung function. Adjusting for body size partially reduced the significance of the observed relationship; adjusting for shared environmental factors did not change the observed results. Parental lung function levels are predictors of the respiratory mechanics of their newborn infants, which can only partially be explained by familial aggregation of body size. This suggests genetic mechanisms in familial aggregation of lung function, which are already detectable early in life.

Coffee and tea consumption and risk of type 2 diabetes.

AIMS/HYPOTHESIS: The aim of this study was to examine the association of consumption of coffee and tea, separately and in total, with risk of type 2 diabetes and which factors mediate these relations. METHODS: This research was conducted as part of the Dutch Contribution to the European Prospective Investigation into Cancer and Nutrition, which involves a prospective cohort of 40,011 participants with a mean follow-up of 10 years. A validated food-frequency questionnaire was used to assess coffee and tea consumption and other lifestyle and dietary factors. The main outcome was verified incidence of type 2 diabetes. Blood pressure, caffeine, magnesium and potassium were examined as possible mediating factors. RESULTS: During follow-up, 918 incident cases of type 2 diabetes were documented. After adjustment for potential confounders, coffee and tea consumption were both inversely associated with type 2 diabetes, with hazard ratios of 0.77 (95% CI 0.63-0.95) for 4.1-6.0 cups of coffee per day (p for trend = 0.033) and 0.63 (95% CI: 0.47-0.86) for >5.0 cups of tea per day (p for trend = 0.002). Total daily consumption of at least three cups of coffee and/or tea reduced the risk of type 2 diabetes by approximately 42%. Adjusting for blood pressure, magnesium, potassium and caffeine did not attenuate the associations. CONCLUSIONS/INTERPRETATION: Drinking coffee or tea is associated with a lowered risk of type 2 diabetes, which cannot be explained by magnesium, potassium, caffeine or blood pressure effects. Total consumption of at least three cups of coffee or tea per day may lower the risk of type 2 diabetes.

Adjustment of treatment increases quality of life in patients with epilepsy: a randomized controlled pragmatic trial.

BACKGROUND AND PURPOSE: Complaints about side-effects of antiepileptic drugs (AEDs) may be overlooked in clinical practice. We assessed the value and risks of an active intervention policy for reported complaints in a randomized controlled pragmatic trial. METHODS: This randomized controlled pragmatic trial included 111 adults treated for epilepsy in seven general hospitals. They were considered well-managed by their treating physician, but reported moderate to severe complaints on a questionnaire (SIDAED, assessing SIDe effects in AED treatment). The intervention was adjustment of AED treatment (53 patients), either reduction of dose or switch of AED, versus continuation of treatment unchanged (58 control patients) during 7 months. Primary outcomes were quality of life (Qolie-10) and complaints score. Secondary outcome measures were the occurrence of seizures or adverse events. RESULTS: After 7 months, the relative risk (RR) for improvement in quality of life was 1.80 (1.04-3.12) for the intervention group compared to control and the RR of decrease in complaints was 1.34 (0.88-2.05). In 58% of patients randomized to adjustment, the medication had indeed been changed. DISCUSSION: In conclusion, despite a possible risk of seizure recurrence, adjustment of drug treatment in well-managed patients with epilepsy, who report considerable complaints, improves the quality of life.

Comparing 6 and 10 sec exhalation time in exhaled nitric oxide measurements in children.

Standard exhalation time for Fractional exhaled Nitric Oxide (FeNO) measurements is 10 sec but this is difficult for young children. Recommended exhalation time for children is 6 sec, but this was never substantiated in literature. We aimed to investigate the agreement between FeNO values measured with exhalation times of 6 and 10 sec and the preference of children for either method. The study population comprised children aged 5-17 years visiting the Pediatric Pulmonology outpatient clinic. FeNO values, measured during 6 (FeNO-6) and 10 (FeNO-10) sec (random order) using the single-breath online (SBOL) technique, were compared. Preferences for exhalation times were related to FVC values. Ninety-eight children (mean age 10.6 years) were included. Median FeNO-6 (15.2 ppb) and FeNO-10 (13.6 ppb) did not differ significantly (P = 0.259). Mean difference between FeNO-6 and FeNO-10 was -0.3 ppb, limits of agreement ranging from -5.8 ppb to +5.3 ppb. Sixty percent of children with a Forced Vital Capacity (FVC) less than 3 L preferred the FeNO-6 method. We found good agreement between FeNO-6 and FeNO-10, so they can be used interchangeably. An exhalation time of 6 sec was preferred by the majority of subjects with a FVC below 3 L.

Quality of life in chronic illness: children, parents and paediatricians have different, but stable perceptions.

AIM: Quality of life assessments can be helpful to estimate the well-being of chronically ill children. The aim of this study was to investigate the differences in perception of health-related quality of life (HRQoL) among children, parents and paediatricians at the time of diagnosis and after initial treatment in four chronic diseases. METHODS: HRQoL was assessed with the Health Utilities Index mark 3 (HUI3). The HUI3 consists of eight attributes (vision, hearing, speech, ambulation, dexterity, emotion, cognition and pain). RESULTS: Nineteen paediatricians and 60 patients (aged 10-17 years) and their parents with newly diagnosed acute lymphoblastic leukaemia, juvenile idiopathic arthritis, asthma or with cystic fibrosis admitted for pneumonia participated in the study. Health and well-being perceptions were clearly different among paediatricians, parents and patients, both at diagnosis and after initial treatment. Perception differences were more prominent in the subjective attributes, emotion and pain. The agreement for these attributes was 23% and 5%, respectively. Paediatricians assessed the patients to have less pain than the patients and parents did. The reverse was true for the attribute emotion. At follow-up, the agreement was higher for the attributes ambulation and pain. CONCLUSION: At the onset of a chronic disease and after initial treatment, paediatricians, parents and children have different perceptions of the child's quality of life, particularly as to the subjective attributes pain and emotion. In view of these differences in perception among patients, their caregivers and paediatricians, this study suggests that whenever possible, multi-respondent assessment of HRQoL should be considered.

Postnatal hydrocortisone treatment for chronic lung disease in the preterm newborn and long-term neurodevelopmental follow-up.

The benefits versus the risks of postnatal administration of steroids in preterm-born infants are still debatable. This review examines the literature on postnatal hydrocortisone treatment for chronic lung disease (CLD) in preterm-born infants with a particular focus on the effects of such treatment on long-term neurodevelopmental outcomes. Quantitative published evidence does not point to a clear advantage of treatment with hydrocortisone over dexamethasone with regard to the impact on long-term neurological outcomes. However, in the absence of a randomised comparison, a consensus may soon have to be reached on the basis of the best available evidence whether hydrocortisone should replace dexamethasone in the treatment of CLD.

Outcomes of hematopoietic stem cell transplantation for Hurler's syndrome in Europe: a risk factor analysis for graft failure.

Hurler's syndrome (HS), the most severe form of mucopolysaccharidosis type-I, causes progressive deterioration of the central nervous system and death in childhood. Allogeneic stem cell transplantation (SCT) before the age of 2 years halts disease progression. Graft failure limits the success of SCT. We analyzed data on HS patients transplanted in Europe to identify the risk factors for graft failure. We compared outcomes in 146 HS patients transplanted with various conditioning regimens and grafts. Patients were transplanted between 1994 and 2004 and registered to the European Blood and Marrow Transplantation database. Risk factor analysis was performed using logistic regression. 'Survival' and 'alive and engrafted'-rate after first SCT was 85 and 56%, respectively. In multivariable analysis, T-cell depletion (odds ratio (OR) 0.18; 95% confidence interval (CI) 0.04-0.71; P=0.02) and reduced-intensity conditioning (OR 0.08; 95% CI 0.02-0.39; P=0.002) were the risk factors for graft failure. Busulfan targeting protected against graft failure (OR 5.76; 95% CI 1.20-27.54; P=0.028). No difference was noted between cell sources used (bone marrow, peripheral blood stem cells or cord blood (CB)); however, significantly more patients who received CB transplants had full-donor chimerism (OR 9.31; 95% CI 1.06-82.03; P=0.044). These outcomes may impact the safety/efficacy of SCT for 'inborn-errors of metabolism' at large. CB increased the likelihood of sustained engraftment associated with normal enzyme levels and could therefore be considered as a preferential cell source in SCT for 'inborn errors of metabolism'.

Passive respiratory mechanics measured during natural sleep in healthy term neonates and infants up to 8 weeks of life.

The single occlusion technique (SOT) is a simple and noninvasive technique for measurement of passive respiratory mechanics in infants. Reference values based on measurements of a large population of healthy infants performed outside specialized research laboratories are lacking. The aim of this study was to present reference values for passive respiratory mechanics based on a large population of healthy term neonates and infants measured during natural sleep in routine care. As part of the ongoing Wheezing Illnesses Study Leidsche Rijn (WHISTLER), the compliance (C(rs)) and resistance (R(rs)) of the respiratory system were measured in 450 healthy unsedated neonates and infants with a mean age of 4.6 +/- 1.3 weeks. Multivariable regression analysis, with gestational age, age at measurement, body size, sex, and ethnicity as possible predictors, was carried out to estimate prediction equations for mean C(rs) and R(rs) values. Technically acceptable lung function measurements could be performed in 328 (73%) neonates and infants. Median C(rs) was 39.5 (range 14.8-79.1) ml/kPa and median R(rs) was 7.4 (range 3.8-19.5) kPa/L/sec. The following regression equations for C(rs) and R(rs) were obtained: ln C(rs) = 1.677 + 1.3 x 10(-4) x birth weight (g) + 0.030 x birth length (cm) and ln R(rs) = 2.496-3.1 x 10(-6) x birth length(3) (cm(3)) - 0.114 x sex. We provided reference values for passive respiratory mechanics using the SOT in a large population of healthy term neonates and infants measured during natural sleep. These data provide a frame of reference for assessing the normality of SOT measurements performed in routine care.

How fatigue is related to other somatic symptoms.

AIMS: To assess the relation between fatigue and somatic symptoms in healthy adolescents and adolescents with chronic fatigue syndrome/myalgic encephalopathy (CFS/ME). METHODS: Seventy two adolescents with CFS were compared within a cross-sectional study design with 167 healthy controls. Fatigue and somatic complaints were measured using self-report questionnaires, respectively the subscale subjective fatigue of the Checklist Individual Strength (CIS-20) and the Children's Somatization Inventory. RESULTS: Healthy adolescents reported the same somatic symptoms as adolescents with CFS/ME, but with a lower score of severity. The top 10 somatic complaints were the same: low energy, headache, heaviness in arms/legs, dizziness, sore muscles, hot/cold spells, weakness in body parts, pain in joints, nausea/upset stomach, back pain. There was a clear positive relation between log somatic symptoms and fatigue (linear regression coefficient: 0.041 points log somatic complaints per score point fatigue, 95% CI 0.033 to 0.049) which did not depend on disease status. CONCLUSIONS: Results suggest a continuum with a gradual transition from fatigue with associated symptoms in healthy adolescents to the symptom complex of CFS/ME.